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Related Experiment Videos

Interactions of gold coordination complexes with DNA.

C K Mirabelli, C M Sung, J P Zimmerman

    Biochemical Pharmacology
    |May 1, 1986
    PubMed
    Summary

    Gold complexes can interact with DNA, causing conformational changes. Gold(III) complexes bind and alter DNA structure, while some gold(I) complexes show specific binding, unlike auranofin.

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    Area of Science:

    • Inorganic Chemistry
    • Biochemistry
    • Molecular Biology

    Background:

    • Gold complexes are investigated for their potential therapeutic applications, including anticancer properties.
    • Understanding the interaction of metal complexes with DNA is crucial for developing novel metallodrugs.
    • The DNA-binding and DNA-modifying capabilities of gold compounds are not fully elucidated.

    Purpose of the Study:

    • To investigate and compare the interactions of gold(I) and gold(III) complexes with plasmid DNA.
    • To elucidate the mechanisms by which gold complexes induce conformational changes in DNA.
    • To compare the DNA-binding activity of gold complexes with that of cisplatin (CDDP).

    Main Methods:

    • Agarose gel electrophoresis was employed to assess DNA-gold complex interactions.

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  • Plasmid pBR322 DNA (supercoiled, relaxed, and open circular forms) was used as the target DNA.
  • Ethidium bromide displacement assay was used to evaluate DNA binding inhibition.

    • Main Results:

    • Trichloro(pyridine)gold(III) demonstrated dose-dependent binding to DNA, inducing conformational changes like unwinding and shortening.
    • Auranofin showed no interaction with DNA, but its analog chloro(triethylphosphine) gold(I) interacted with DNA at pH 9.5.
    • The binding of chloro(triethylphosphine) gold(I) was inhibited by the thiosugar moiety of auranofin, suggesting preferential gold-ligand interaction.
    • Several gold compounds inhibited ethidium bromide binding to DNA, confirming their interaction with DNA.

    Conclusions:

    • Gold complexes can bind to DNA and induce significant conformational alterations.
    • Gold(I) and gold(III) complexes may interact with DNA through distinct chemical mechanisms, leading to varied conformational changes.
    • The coordinating ligands in gold complexes, such as chloride, bromide, and thiocyanate, can be exchanged for DNA binding sites.